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Adequacy of Hemodialysis Data from HENNET. นพ. ธนชัย พนาพุฒิ อายุรแพทย์โรคไต รพศ. ขอนแก่น 5 กค. 2556.

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Presentation on theme: "Adequacy of Hemodialysis Data from HENNET. นพ. ธนชัย พนาพุฒิ อายุรแพทย์โรคไต รพศ. ขอนแก่น 5 กค. 2556."— Presentation transcript:

1 Adequacy of Hemodialysis Data from HENNET. นพ. ธนชัย พนาพุฒิ อายุรแพทย์โรคไต รพศ. ขอนแก่น 5 กค. 2556

2 HENNET project HEmodialysis Network of the North-East of Thailand นพ. ธนชัย พนาพุฒิ นพ. จิรศักดิ์ อนุกุลกนันต์ชัย รพ. ขอนแก่น รศ. นพ. ทวี ศิริวงศ์ รศ. นพ. ชลธิป พงศ์สกุล รศ. พญ. ศิริรัตน์ เรืองจุ้ย รพ. ศรีนครินทร์ นพ. พิสิฐ อินทรวงษ์โชติ รพ. หนองคาย นพ. สุรพงษ์ นเรนทร์พิทักษ์รพ. อุดรธานี นพ. สัจจะ ตติยานุพันธ์วงศ์ รพ. ชัยภูมิ พญ. ลักษมณ ประเดิมรพ. ร้อยเอ็ด นพ. ชวศักดิ์ กนกกัณฑ์พงษ์ รพ. มหาราชนครราชสีมา พญ. กรรณิการ์ นิวัตยกุล รพ. เลย นพ. ปกรณ์ ตุงคะเสรีรักษ์ รพ. สุรินทร์ นพ. อมฤต สุวัฒนศิลป์ รพ. มหาสารคาม พญ. ทัดสะรัง แก้วบุนมา รพ. ท่าบ่อ

3 Agenda What is Adequacy of HD Data from HENNET Project Kt/V: Do we really need it ?

4 Dr. John T. Daugirdas Dr. Daugirdas is Professor of Medicine at the University of Illinois at Chicago.

5 What is Adequacy of Hemodialysis ? Adequacy of dialysis refers to how well we remove toxins and waste products from the patient’s blood, and has a major impact on their well-being.

6 How do we know if a Patient is Adequately Dialyzed ? Urea Kinetic Modeling Why can’t I understand it ? It can’t be that difficult !

7 MW 60, only slightly toxic per se a MARKER for small MW uremic toxins Urea removal other small toxin removal WHY UREA ?

8 MW 60, only slightly toxic per se a MARKER for small MW uremic toxins Urea removal other small toxin removal g = rate of UREA generation g protein catabolic rate (PCR) PCR dietary protein intake ? g can be derived from pre and post BUN WHY UREA ?

9 Monitoring the patient’s urea Predialysis BUN or Time-averaged BUN BAD if HIGH, also BAD if too LOW! Reflect balance of urea removal vs. production BUNpre BUNpost BUN (mg/dl) Time (hour)

10 Monitoring the patient’s urea Predialysis BUN or Time-averaged BUN BAD if HIGH, also BAD if too LOW! Reflect balance of urea removal vs. production BUNpre BUNpost BUN (mg/dl) Time (hour)

11 TAC BUN Monitoring the patient’s urea Predialysis BUN or Time-averaged BUN BAD if HIGH, also BAD if too LOW! Reflect balance of urea removal vs. production BUNpre BUNpost BUN (mg/dl) Time (hour)

12 URR or Kt/V URR% : (Upre – Upost) x 100 Upre Reflect removal of urea and other toxins PRIMARY monitors of dialysis adequacy Monitoring the patient’s urea

13 Kt/V = fractional urea clearance K = dialyzer clearance (ml/min or L/hr) t = time (min or hr) V = distribution volume of urea (ml or L) K x t = L/hr x hr = LITERS V = LITERS Kt/V = LITERS/LITERS = ratio What is Kt/V ?

14 K. t V = 40 liters BUN = 0 BUN = 80 Holding Tank Model K = 10 L/Hr

15 K. t V = 40 liters BUN = 0 BUN = 80 Holding Tank Model Kt/V URR

16 V = 40 liters K t = BUN = 0 BUN = L

17 V = 40 liters K t = BUN = 0 BUN = 80 Kt/V = 20 / 40 = L

18 V = 40 liters K t = BUN = 0 BUN = 80 Kt/V = 20 / 40 = 0.50 Post BUN = 40 URR = (pre-post) / pre = (80-40) / 80 = L

19 V = 40 liters BUN = 0 BUN = 80, 70, 60 Dialyzer outlet fluid returned continually during dialysis K. t

20 Relationship between Kt/V and URR

21 spKt/V = single pool eqKt/V = equilibrated (Double pool) Std Kt/V = weekly standard Kt/V

22 Post-Dialysis rebound

23 Equilibrated Kt/V

24 spKt/V = single pool eqKt/V = equilibrated (Double pool) Std Kt/V = weekly standard Kt/V

25 What is the target spKt/V in 2 times/week HD patients ?

26 K/DOQI 2006: Minimum spKt/V ScheduleKr<2 ml/min/1.73m2 Kr>2 ml/min/1.73m2 2x/wk Not recommended 2.0* 3x/wk x/wk x/wk Dialyzer clearance only *not recommended unless Kr > 3 K/DOQI CPG for Hemodialysis Adequacy: update Am J Kidney Dis 2007; 37: S7-S64.

27 K/DOQI : Methods for Post Dialysis Blood Sampling 1.Both samples should be drawn during the same session. 2.Predialysis BUN should be drawn before treatment began. 3.Postdialysis BUN, Avoid access recirculation by Slow flow to 100 ml/min for 15 seconds K/DOQI CPG for Hemodialysis Adequacy: update Am J Kidney Dis 2007; 37: S7-S64.

28 Data from HENNET. Exploring Mortality based on Kt/V among ESRD patients undergoing Twice-weekly Hemosialysis

29 Setting 11 hemodialysis centers Accrual period 3 months from Feb Follow up period 1 years HENNET * * ** * * * * * * * Multi-center cohort study

30 Part1 Baseline Part2 Follow up Part3 Hospitalization note Part4 Discharge summary

31 Enrollment HD 2/wk Lab record 2 monthly Outcomes: Disease-related Death Study design overview Inclusion Age 18 – 80 years HD > 3 months. Exclusion Pregnancy, Breast feeding Advance malignancy Bed-ridden status 1 year HENNET Censor: Kidney transplantation Shift to peritoneal dialysis Refer to other centers Change frequency Death from accident

32 Enrollment 504 HD 2/wk Death 33 Results 1 year 6,928 patients-months were observed. Mortality rate 4.8 / 1,000 patient-months. HENNET

33 Table1. Baseline characteristics CharactersSurvivors N=471 Non-survivors N=33 Male276 (58.6%)15 (45.5%) Age, year54.9 ± ± 10.6 Married365 (77.5%)24 (72.7%) ICED score1.2 ± ± 0.9 Causes of ESRD Diabetes Hypertension Glomerulonephritis Obstructive uropathy Gout Cystic disease Unknown 144 (30.6) 90 (19.1) 31 (6.6) 29 (6.2) 28 (5.9) 6 (1.3) 142 (30.2) 16 (48.5) 8 (24.2) 1 (3) - 3 (9.1) - 5 (15.2) Time on HD, month40.6 ± ± 28.0 Anuria (<100ml/day)228 (48.4%)15 (45.5%) HENNET

34 Kt/V by Age 1.7±0.31.7±0.4 HENNET

35 Distribution of Kt/V Mean 1.7±0.3 Range 0.67 – 2.83 HENNET

36 Distribution of Kt/V Adequate HD 20.6% Mean 1.7±0.3 Range 0.67 – 2.83 HENNET

37 Hemodialysis patients with adequate dialysis (URR>65%) CMS ESRD Clinical Performance Measures Project, Centers for Medicare & Medicaid Services, ESRD Clinical Performance Measures Project,

38 Kt/V among women and men HENNET Women 214(42.5%) Men 290(57.5%) Kt/V 1.9±0.3 P < ±0.3

39 > 20 < 15 No. of Reuse 15 N Kt/V by numbers of Dialyzer Reuse % % Range 0 – 30 HENNET

40 > 20 < 15 No. of reuse 15 N Kt/V by numbers of Dialyzer Reuse Kt/V HENNET

41 Prediction of Dead by numbers of Dialyzer Reuse < > 20 Dead rate No. of Reuse HENNET

42 Hemodialysis Prescription Determines Adequacy Hemodialysis component: – Duration of Treatment – Dialyzer Urea Clearance (KOA) – Blood Flow – Dialysate Flow – Heparinization – Access Adequacy of Treatment is Everyone’s Concern !

43 Improving Adequacy of Hemodialysis: It Takes a Team.

44 Kt/V : Do we really need it ?

45 N = < p= p= (rel) 0.69 p= p=0.01 RR Mortality Risk by Kt/V Categorical and Linear Estimates, RR = 0.93 / 0.1 Kt/V ( p < 0.01) RR = 0.93 / 0.1 Kt/V ( p < 0.01) Kt/V Delivered Kt/V* (Quintiles) * From the Pre/Post BUN and Pre/Post Weight. N = 2,311, Thrice Weekly only.

46 P = 0.53

47 Kt/V among survivors and non-survivors HENNET SurvivorsNon-survivors Kt/V 1.65 ( ) 1.7 ( ) P=0.52

48 Log rank test, P=0.41 Kt/V > 2 Kt/V < 2 HENNET

49 Log rank test, P=0.41 Kt/V > 2 Kt/V < 2 HENNET 1 year survival 94%

50 Kt/V > 2 Kt/V < 2 HR 1.64 ( ), p=0.5* DM Non DM Kt/V > 2 Kt/V < 2 Survival probability among patients with Kt/V>2 and <2 according to diabetic status HR 1.0 ( ), p=0.9* *adjusted for age HENNET

51 – – – – 2.83 Kt/V Hazard ratio of death Relative Risk of Death by Kt/V quartiles HENNET

52 Figure 15. Cox proportional hazard ratios and their 95% CI, adjusted for age, among women undergoing twice-weekly HD with Kt/V 1.4, 1.6, 1.8, 2.0, 2.2. HENNET

53 FactorsUnadjusted HRAdjusted HR95%CIP-value* Kt/V, per 1 unit decrease † 1.2‡ 1.4¶ Serum albumin, per 1 g/dl decrease Current smoker < Table 9. Unadjusted and adjusted hazard ratio of death using Cox regression model. *P-value from partial likely hood ratio test, adjusted for age, ICED, time on dialysis and dialysis centers. † Adjusted HR considering effect of albumin level ‡ Adjusted HR considering effect of smoking ¶Adjusted HR considering effects of albumin level and smoking Prognostic factors of Deaths

54 Kt/V : Do we really need it ? May be, there are stronger predictors of mortality.

55 Take Home Message !! 1. Adequacy of dialysis is based on Kt/V and URR.

56 Take Home Message !! 1. Adequacy of dialysis is based on Kt/V and URR. 2. Kt/V and URR are mathematically linked.

57 Take Home Message !! 1. Adequacy of dialysis is based on Kt/V and URR. 2. Kt/V and URR are mathematically linked. 3. For HD 2/week: Target spKt/V 2, Kr > 2 ml/min/1.73m 2

58 Take Home Message !! 1. Adequacy of dialysis is based on Kt/V and URR. 2. Kt/V and URR are mathematically linked. 3. For HD 2/week: Target spKt/V 2, Kr > 2 ml/min/1.73m 2 4. For HD 3/week: Target spKt/V 1.2, URR>65%.

59 5. Data from – Only 20.6% is adequately dialyzed, Kt/V>2. HENNET Take Home Message !!

60 5. Data from – Only 20.6% is adequately dialyzed, Kt/V>2. – Mean Kt/V of women is significantly higher than that of men. HENNET Take Home Message !!

61 5. Data from – Only 20.6% is adequately dialyzed, Kt/V>2. – Mean Kt/V of women is significantly higher than that of men. – Increase No. of Reuse related to an increase mortality in a linear prediction. HENNET Take Home Message !!

62 5. Data from – Only 20.6% is adequately dialyzed, Kt/V>2. – Mean Kt/V of women is significantly higher than that of men. – Increase No. of Reuse related to an increase mortality in a linear prediction. – Higher Kt/V quartiles trend to have lower RR for death. HENNET Take Home Message !!

63 5. Data from – Only 20.6% is adequately dialyzed, Kt/V>2. – Mean Kt/V of women is significantly higher than that of men. – Increase No. of Reuse related to an increase mortality in a linear prediction. – Higher Kt/V quartiles trend to have lower RR for death. – Suggested target Kt/V > 1.8 for Thai women on 2HD/wk. HENNET Take Home Message !!

64 5. Data from – Only 20.6% is adequately dialyzed, Kt/V>2. – Mean Kt/V of women is significantly higher than that of men. – Increase No. of Reuse related to an increase mortality in a linear prediction. – Higher Kt/V quartiles trend to have lower RR for death. – Suggested target Kt/V > 1.8 for Thai women on 2HD/wk. – Predictors of death are SMOKING and ALBUMIN level. HENNET Take Home Message !!

65 6. spKt/V is a current marker for monitoring HD adequacy. Take Home Message !!

66 Acknowledgements : Grant supports The Royal College of Physician of Thailand The Medical Association of Thailand The Kidney Foundation of Thailand

67 Thank you for your attention

68 Cox proportional hazard ratios and their 95% CI, adjusted for age, among patients With Kt/V 1.4, 1.6, 1.8, 2.0, 2.2. HENNET

69 Kt/V by BMI classes Underweight Obese Normal Overweight > 30 < 18.5 BMI Percent HENNET

70 Kt/V by BMI classes Underweight Obese Normal Overweight > 30 < 18.5 BMI Kt/V P=0.00 HENNET

71 Factors affect spKt/V Kt/V>1.7 N=245(48.6%) Kt/V<1.7 N=259(51.4%) P BMI, kg/m ± ± Incidence HD, < 12 mo.23 (9.4%)45 (17.4%)0.01 Dialyzer membrane: Semi-synthetic99 (40.4%)101 (39%)0.75 Low Flux Dialyzer82 (33.5%)97 (34.5%)0.35 Dialyzer Surface area1.76±0.21.8± No. of Dialyzer Reuse17.1± ± Blood Flow, ml/min324.2± ± Dialysate flow, ml/min537.9± ± DM71 (28.9%)107 (60.1%)0.00 Current Smoking5 (2.0%)12 (4.6%)0.08 P<0.05 HENNET

72 Factors affect spKt/V Kt/V>1.7 N=245(48.6%) Kt/V<1.7 N=259(51.4%) P BMI, kg/m ± ± * Incidence HD, < 12 mo.23 (9.4%)45 (17.4%)0.01 Dialyzer membrane: Semi-synthetic99 (40.4%)101 (39%)0.75 Low Flux Dialyzer82 (33.5%)97 (34.5%)0.35 Dialyzer Surface area1.76±0.21.8± No. of Dialyzer Reuse17.1± ± * Blood Flow, ml/min324.2± ± * Dialysate flow, ml/min537.9± ± DM71 (28.9%)107 (60.1%)0.00 Current Smoking5 (2.0%)12 (4.6%)0.08 *P<0.05 in Multivariate Analysis HENNET

73 Factors affect spKt/V Coef.95%CIP BMI, kg/m to No. of Dialyzer Reuse to Blood Flow, ml/min to Kt/V < 1.7 Every 1 increase in BMI will increase 20% of Kt/V<1.7 HENNET

74 NIH Hemo Study URR of about 67% vs. about 75% spKt/V of 1.3 vs. 17 eKt/V of about 1.05 vs Also will compare small-pore (low-flux) vs. large-pore (high flux) membranes Endpoints: mortality, hospitalization, fall in dry weight

75 HD adequacy : dose K/DOQI CPG for Hemodialysis Adequacy: update Am J Kidney Dis 2007; 37: S7-S64. K: dialyzer clearance t: duration of HD V: volume distribution of urea

76 Post-Dialysis rebound

77

78 Relationship of eKt/V to spKt/V eKt/V = spKt/V [(t/(t+C)] C=35 min if artery, 22 min if vein

79 Std Kt/V, spKt/V and Dialysis frequencies per week

80 Associated causes of death Causes of DeathN% Cardiovascular Infection Cerebrovascular2 6.1 Malignancy2 6.1 Other GI bleeding Bleeding diverticulosis Dialysis withdrawal Car accident

81 Outcomes N% Death Refer to other centers Change frequency Shift to CAPD Kidney transplantation6 6.3 Loss to follow up6 6.3

82 Indices of Urea Removal Kt/V Reflects urea removal NCDS suggested Kt/V must be > 0.90 Population studies suggest Kt/V should be> 1.2 URR Also reflects urea removal Current goal is a URR > 65 %

83

84

85 Sample

86

87

88 < Approximate Kt/V Relative Mortality Risk R (post / pre BUN) >

89 Percent 1.5 P=1.00 Incidence and Prevalence Hemodialysis Incidence HD <= 12 mo. Prevalence HD > 12 mo. (13.5%) (86.5%) HENNET

90 Kt/V (1.46 to 1.61) P=0.00 Kt/V by Incidence and Prevalence Hemodialysis Incidence HD <= 12 mo. Prevalence HD > 12 mo (1.69 to 1.74) HENNET


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